Andrieu Nadine, Goldgar David E, Easton Douglas F, Rookus Matti, Brohet Richard, Antoniou Antonis C, Peock Susan, Evans Gareth, Eccles Diana, Douglas Fiona, Noguès Catherine, Gauthier-Villars Marion, Chompret Agnès, Van Leeuwen Flora E, Kluijt Irma, Benitez Javier, Arver Brita, Olah Edith, Chang-Claude Jenny
INSERM, Emi00-06, Service de Biostatistique, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
J Natl Cancer Inst. 2006 Apr 19;98(8):535-44. doi: 10.1093/jnci/djj132.
Multiparity, young age at first childbirth, and breast-feeding are associated with a reduced risk of breast cancer in the general population. The breast cancer predisposition gene, BRCA1, regulates normal cell differentiation. Because mammary gland cells divide and differentiate during pregnancy, reproductive factors may influence breast cancer risk in BRCA1/2 mutation carriers differently than they do in noncarriers.
We performed a retrospective cohort study of 1601 women in the International BRCA1/2 Carrier Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2. Information on reproductive factors was obtained from a questionnaire. At the time of interview 853 subjects were classified with breast cancer. Data were analyzed by using a weighted cohort approach. All statistical tests were two-sided.
There was no statistically significant difference in the risk of breast cancer between parous and nulliparous women. Among parous women, an increasing number of full-term pregnancies was associated with a statistically significant decrease in the risk of breast cancer (Ptrend = .008); risk was reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional birth. This association was the same for carriers of mutations in either BRCA1 or BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation carriers, first childbirth at later ages was associated with an increased risk of breast cancer compared with first childbirth before age 20 years (20-24 years, hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI = 1.02 to 7.07]; > or = 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in BRCA1 mutation carriers, first childbirth at age 30 years or later was associated with a reduced risk of breast cancer compared with first childbirth before age 20 years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted pregnancies (induced abortions or miscarriage) nor history of breast-feeding was statistically significantly associated with the risk of breast cancer.
BRCA1 and BRCA2 mutation carriers older than 40 years show a similar reduction in breast cancer risk with increasing parity as non-carriers.
在普通人群中，多产、首次生育年龄较小以及母乳喂养与患乳腺癌风险降低相关。乳腺癌易感基因BRCA1可调节正常细胞分化。由于乳腺细胞在孕期会进行分裂和分化，生殖因素对BRCA1/2突变携带者患乳腺癌风险的影响可能与非携带者不同。
我们在国际BRCA1/2携带者队列研究中对1601名女性进行了一项回顾性队列研究，所有参与者均携带BRCA1或BRCA2突变。通过问卷调查获取生殖因素信息。在访谈时，853名受试者被诊断为乳腺癌。采用加权队列方法进行数据分析。所有统计检验均为双侧检验。
经产妇和未产妇患乳腺癌的风险在统计学上无显著差异。在经产妇中，足月妊娠次数增加与患乳腺癌风险在统计学上显著降低相关（趋势P值=0.008）；每增加一次生育，风险降低14%（95%置信区间[CI]=6%至22%）。BRCA1或BRCA2突变携带者的这种关联相同，且仅限于40岁以上女性。在BRCA2突变携带者中，与20岁之前首次生育相比，20 - 24岁首次生育患乳腺癌风险增加（风险比[HR]=2.33[95%CI=0.93至5.83]）；25 - 29岁首次生育，HR=2.68[95%CI=1.02至7.07]；≥30岁首次生育，HR=1.97[95%CI=0.67至5.81]），而在BRCA1突变携带者中，与20岁之前首次生育相比，30岁及以后首次生育患乳腺癌风险降低（HR=0.58[95%CI=0.36至0.94]）。既往有终止妊娠史（人工流产或自然流产）和母乳喂养史与患乳腺癌风险在统计学上均无显著关联。
40岁以上的BRCA1和BRCA2突变携带者与非携带者一样，随着产次增加，患乳腺癌风险有类似程度的降低。
